{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:21:47Z","timestamp":1793161307085,"version":"4.5.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020410","name":"T\u00fcrkiye Sa\u011fl\u0131k Enstit\u00fcleri Ba\u015fkanl\u0131\u011f\u0131","doi-asserted-by":"publisher","award":["4235"],"award-info":[{"award-number":["4235"]}],"id":[{"id":"10.13039\/100020410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-50210-0","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:56:56Z","timestamp":1777046216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthesis, characterization, biological evaluation, and molecular modeling of novel nimesulide urea derivatives as potential MetAP2 inhibitors"],"prefix":"10.1038","volume":"16","author":[{"given":"\u00d6zg\u00fcr","family":"Y\u0131lmaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u011fmur","family":"Biliz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Kulo\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fcbra","family":"Aranc\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer","family":"Erdo\u011fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zge","family":"\u00c7evik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcfide","family":"Karahasano\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naz Mina Mert","family":"\u015eahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe Buse","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilge","family":"Tuzcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemal","family":"Yelek\u00e7i","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015e. G\u00fcniz","family":"K\u00fc\u00e7\u00fckg\u00fczel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"50210_CR1","doi-asserted-by":"publisher","unstructured":"Bianchi, M. et al. Clinical applications of nimesulide in pain, arthritic conditions and fever. In (ed. Rainsford, K. D.) Nimesulide\u2014Actions and Uses 245\u2013313 (Birkh\u00e4user Basel, 2005). https:\/\/doi.org\/10.1007\/3-7643-7410-1_5.","DOI":"10.1007\/3-7643-7410-1_5"},{"key":"50210_CR2","doi-asserted-by":"publisher","first-page":"4304","DOI":"10.1016\/j.bmc.2017.06.009","volume":"25","author":"M Catarro","year":"2017","unstructured":"Catarro, M. et al. Novel 4-acetamide-2-alkylthio-N-acetanilides resembling nimesulide: Synthesis, cell viability evaluation and in silico studies. Bioorg. Med. Chem. 25, 4304\u20134313. https:\/\/doi.org\/10.1016\/j.bmc.2017.06.009 (2017).","journal-title":"Bioorg. Med. Chem."},{"key":"50210_CR3","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1211\/0022357001774255","volume":"52","author":"AK Singla","year":"2000","unstructured":"Singla, A. K., Chawla, M. & Singh, A. Nimesulide some pharmaceutical and pharmacological aspects\u2014an update. J. Pharm. Pharmacol. 52, 467\u2013486. https:\/\/doi.org\/10.1211\/0022357001774255 (2000).","journal-title":"J. Pharm. Pharmacol."},{"key":"50210_CR4","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.2165\/00002018-200124140-00006","volume":"24","author":"A Conforti","year":"2001","unstructured":"Conforti, A., Leone, R., Moretti, U., Mozzo, F. & Velo, G. Adverse drug reactions related to the use of NSAIDs with a focus on nimesulide: Results of spontaneous reporting from a Northern Italian area. Drug Saf. 24, 1081\u20131090. https:\/\/doi.org\/10.2165\/00002018-200124140-00006 (2001).","journal-title":"Drug Saf."},{"key":"50210_CR5","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1185\/030079906X104849","volume":"22","author":"K Rainsford","year":"2006","unstructured":"Rainsford, K. D. Nimesulide\u2014a multifactorial approach to inflammation and pain: Scientific and clinical consensus. Curr. Med. Res. Opin. 22, 1161\u20131170. https:\/\/doi.org\/10.1185\/030079906X104849 (2006).","journal-title":"Curr. Med. Res. Opin."},{"key":"50210_CR6","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1023\/B:DDAS.0000034553.58554.ab","volume":"49","author":"Y Baoping","year":"2004","unstructured":"Baoping, Y. et al. Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt\/PKB activation in gastric cancer cell line. Dig. Dis. Sci. 49, 948\u2013953. https:\/\/doi.org\/10.1023\/B:DDAS.0000034553.58554.ab (2004).","journal-title":"Dig. Dis. Sci."},{"key":"50210_CR7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.amjoto.2013.10.009","volume":"35","author":"Z Liang","year":"2014","unstructured":"Liang, Z. et al. Effect of nimesulide on the growth of human laryngeal squamous cell carcinoma. Am. J. Otolaryngol. Head Neck Med. Surg. 35, 120\u2013129. https:\/\/doi.org\/10.1016\/j.amjoto.2013.10.009 (2014).","journal-title":"Am. J. Otolaryngol. Head Neck Med. Surg."},{"key":"50210_CR8","doi-asserted-by":"publisher","first-page":"102966","DOI":"10.1016\/j.bioorg.2019.102966","volume":"88","author":"M Catarro","year":"2019","unstructured":"Catarro, M., Serrano, J. L., Ramos, S. S., Silvestre, S. & Almeida, P. Nimesulide analogues: From anti-inflammatory to antitumor agents. Bioorg. Chem. 88, 102966. https:\/\/doi.org\/10.1016\/j.bioorg.2019.102966 (2019).","journal-title":"Bioorg. Chem."},{"key":"50210_CR9","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S1590-8658(03)00272-X","volume":"35","author":"B Buecher","year":"2003","unstructured":"Buecher, B. et al. Molecular mechanisms involved in the antiproliferative effect of two COX 2 inhibitors, nimesulide and NS-398, on colorectal cancer cell lines. Dig. Liver Dis. 35, 557\u2013565. https:\/\/doi.org\/10.1016\/S1590-8658(03)00272-X (2003).","journal-title":"Dig. Liver Dis."},{"key":"50210_CR10","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/S0014-5793(02)03535-4","volume":"531","author":"R Yamazaki","year":"2002","unstructured":"Yamazaki, R., Kusunoki, N., Matsuzaki, T., Hashimoto, S. & Kawai, S. Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells. FEBS Lett. 531, 278\u2013284. https:\/\/doi.org\/10.1016\/S0014-5793(02)03535-4 (2002).","journal-title":"FEBS Lett."},{"key":"50210_CR11","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1093\/carcin\/bgh184","volume":"25","author":"E Cheong","year":"2004","unstructured":"Cheong, E. et al. Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell cycle arrest. Carcinogenesis 25, 1945\u20131952. https:\/\/doi.org\/10.1093\/carcin\/bgh184 (2004).","journal-title":"Carcinogenesis"},{"key":"50210_CR12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1097\/00006676-200301000-00007","volume":"26","author":"G Eibl","year":"2003","unstructured":"Eibl, G., Reber, H. A., Wente, M. N. & Hines, O. J. The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2. Pancreas 26, 33\u201341. https:\/\/doi.org\/10.1097\/00006676-200301000-00007 (2003).","journal-title":"Pancreas"},{"key":"50210_CR13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.lungcan.2005.10.015","volume":"51","author":"S Han","year":"2006","unstructured":"Han, S. & Roman, J. COX-2 inhibitors suppress lung cancer cell growth by inducing p21 via COX-2-independent signals. Lung Cancer. 51, 283\u2013296. https:\/\/doi.org\/10.1016\/j.lungcan.2005.10.015 (2006).","journal-title":"Lung Cancer"},{"key":"50210_CR14","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3748\/wjg.v9.i5.915","volume":"9","author":"JY Li","year":"2003","unstructured":"Li, J. Y., Wang, X. Z., Chen, F. L., Yu, J. P. & Luo, H. S. Nimesulide inhibits proliferation via induction of apoptosis and cell cycle arrest in human gastric adenocarcinoma cell line. World J. Gastroenterol. 9, 915\u2013920. https:\/\/doi.org\/10.3748\/wjg.v9.i5.915 (2003).","journal-title":"World J. Gastroenterol."},{"key":"50210_CR15","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1111\/j.1349-7006.2000.tb01030.x","volume":"91","author":"S Nakatsugi","year":"2000","unstructured":"Nakatsugi, S. et al. Chemoprevention by nimesulide, a selective cyclooxygenase-2 inhibitor, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary gland carcinogenesis in rats. Jpn J. Cancer Res. 91, 886\u2013892. https:\/\/doi.org\/10.1111\/j.1349-7006.2000.tb01030.x (2000).","journal-title":"Jpn J. Cancer Res."},{"key":"50210_CR16","doi-asserted-by":"publisher","first-page":"967","DOI":"10.3109\/14756366.2014.1001756","volume":"30","author":"\u00d6 Y\u0131lmaz","year":"2015","unstructured":"Y\u0131lmaz, \u00d6. et al. Synthesis of pro-apoptotic indapamide derivatives as anticancer agents. J. Enzyme Inhib. Med. Chem. 30, 967\u2013980. https:\/\/doi.org\/10.3109\/14756366.2014.1001756 (2015).","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"50210_CR17","doi-asserted-by":"publisher","first-page":"265","DOI":"10.26650\/istanbuljpharm.2022.1094112","volume":"52","author":"\u0130 Atl\u0131han","year":"2022","unstructured":"Atl\u0131han, \u0130., Ko\u00e7yi\u011fit Sevin\u00e7, S., Orun, O., Y\u0131lmaz, \u00d6. & K\u00fc\u00e7\u00fckg\u00fczel, \u015e. G. Mega Tiber, P. Effect of flurbiprofen derivative (SGK597) on cell proliferation and apoptosis of breast cancer cell lines. \u0130stanbul J. Pharm. 52, 265\u2013270. https:\/\/doi.org\/10.26650\/istanbuljpharm.2022.1094112 (2022).","journal-title":"\u0130stanbul J. Pharm."},{"key":"50210_CR18","doi-asserted-by":"publisher","first-page":"184","DOI":"10.25135\/acg.oc.91.20.11.1913","volume":"13","author":"H Yani","year":"2020","unstructured":"Yani, H. et al. Synthesis, cytotoxic activities and molecular modeling studies of some 2-aminonaphtho[2,3-d][1,3]thiazole-4,9-dione derivatives. Org. Commun. 13, 184\u2013193. https:\/\/doi.org\/10.25135\/acg.oc.91.20.11.1913 (2020).","journal-title":"Org. Commun."},{"key":"50210_CR19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.25135\/acg.oc.86.20.09.1802","volume":"13","author":"C K\u00f6se","year":"2020","unstructured":"K\u00f6se, C. et al. Design and synthesis of novel peptidomimetics for cancer immunotherapy. Org. Commun. 13, 89\u2013102. https:\/\/doi.org\/10.25135\/acg.oc.86.20.09.1802 (2020).","journal-title":"Org. Commun."},{"key":"50210_CR20","doi-asserted-by":"publisher","first-page":"735","DOI":"10.2174\/1573406415666190613162322","volume":"16","author":"\u00d6 Y\u0131lmaz","year":"2020","unstructured":"Y\u0131lmaz, \u00d6. et al. Synthesis, anticancer activity on prostate cancer cell lines and molecular modeling studies of flurbiprofen-thioether derivatives as potential target of MetAP (type II). Med. Chem. 16, 735\u2013749. https:\/\/doi.org\/10.2174\/1573406415666190613162322 (2020).","journal-title":"Med. Chem."},{"key":"50210_CR21","doi-asserted-by":"publisher","first-page":"483","DOI":"10.3748\/wjg.v8.i3.483","volume":"23","author":"G Tian","year":"2002","unstructured":"Tian, G. & Yu, J. The effect of nimesulide on proliferation and apoptosis of SMMC-7721 cells. Med. J. Wuhan Univ. 23, 483. https:\/\/doi.org\/10.3748\/wjg.v8.i3.483 (2002).","journal-title":"Med. J. Wuhan Univ."},{"key":"50210_CR22","doi-asserted-by":"publisher","first-page":"111555","DOI":"10.1016\/j.cbi.2025.111555","volume":"416","author":"\u00d6 Y\u0131lmaz","year":"2025","unstructured":"Y\u0131lmaz, \u00d6. et al. Design and synthesis of thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen as potential MetAP (type II) inhibitors. Chem. Biol. Interact. 416, 111555. https:\/\/doi.org\/10.1016\/j.cbi.2025.111555 (2025).","journal-title":"Chem. Biol. Interact."},{"key":"50210_CR23","doi-asserted-by":"publisher","first-page":"112841","DOI":"10.1016\/j.ejmech.2020.112841","volume":"208","author":"K Birg\u00fcl","year":"2020","unstructured":"Birg\u00fcl, K. et al. Synthesis, molecular modeling, in vivo study and anticancer activity against prostate cancer of (+)-(S)-naproxen derivatives. Eur. J. Med. Chem. 208, 112841. https:\/\/doi.org\/10.1016\/j.ejmech.2020.112841 (2020).","journal-title":"Eur. J. Med. Chem."},{"key":"50210_CR24","first-page":"2006","volume":"6","author":"T Hida","year":"2000","unstructured":"Hida, T. et al. Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines. Clin. Cancer Res. 6, 2006\u20132011 (2000).","journal-title":"Clin. Cancer Res."},{"key":"50210_CR25","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1111\/j.1600-0714.2004.00216.x","volume":"33","author":"M Pelzmann","year":"2004","unstructured":"Pelzmann, M., Thurnher, D., Gedlicka, C., Martinek, H. & Knerer, B. Nimesulide and indomethacin induce apoptosis in head and neck cancer cells. J. Oral Pathol. Med. 33, 607\u2013613. https:\/\/doi.org\/10.1111\/j.1600-0714.2004.00216.x (2004).","journal-title":"J. Oral Pathol. Med."},{"key":"50210_CR26","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.ejmech.2011.11.012","volume":"47","author":"B Zhong","year":"2012","unstructured":"Zhong, B. et al. From COX-2 inhibitor nimesulide to potent anti-cancer agent: Synthesis, in vitro, in vivo and pharmacokinetic evaluation. Eur. J. Med. Chem. 47, 432\u2013444. https:\/\/doi.org\/10.1016\/j.ejmech.2011.11.012 (2012).","journal-title":"Eur. J. Med. Chem."},{"key":"50210_CR27","doi-asserted-by":"publisher","first-page":"3591","DOI":"10.1016\/j.ejmech.2009.02.030","volume":"44","author":"S Karaku\u015f","year":"2009","unstructured":"Karaku\u015f, S. et al. Synthesis, antiviral and anticancer activity of some novel thioureas derived from N-(4-nitro-2-phenoxyphenyl)methanesulfonamide. Eur. J. Med. Chem. 44, 3591\u20133595. https:\/\/doi.org\/10.1016\/j.ejmech.2009.02.030 (2009).","journal-title":"Eur. J. Med. Chem."},{"key":"50210_CR28","doi-asserted-by":"publisher","first-page":"132739","DOI":"10.1016\/j.molstruc.2022.132739","volume":"1259","author":"K Birg\u00fcl","year":"2022","unstructured":"Birg\u00fcl, K. et al. Synthesis and molecular modeling of MetAP2 of thiosemicarbazides, 1,2,4-triazoles and thioethers derived from (S)-naproxen as possible breast cancer agents. J. Mol. Struct. 1259, 132739. https:\/\/doi.org\/10.1016\/j.molstruc.2022.132739 (2022).","journal-title":"J. Mol. Struct."},{"key":"50210_CR29","first-page":"769","volume":"12","author":"Y Pan","year":"2003","unstructured":"Pan, Y., Zhang, J. S., Gazi, M. H. & Young, C. Y. F. The cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs celecoxib and nimesulide inhibit androgen receptor activity via induction of c-Jun in prostate cancer cells. Cancer Epidemiol. Biomarkers Prev. 12, 769\u2013774 (2003).","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"50210_CR30","doi-asserted-by":"publisher","first-page":"e0209264","DOI":"10.1371\/journal.pone.0209264","volume":"14","author":"J Kwon","year":"2019","unstructured":"Kwon, J., Kim, S., Yoo, H. & Lee, E. Nimesulide-induced hepatotoxicity: A systematic review and meta-analysis. PLoS One. 14, e0209264. https:\/\/doi.org\/10.1371\/journal.pone.0209264 (2019).","journal-title":"PLoS One"},{"key":"50210_CR31","doi-asserted-by":"publisher","first-page":"113566","DOI":"10.1016\/j.ejmech.2021.113566","volume":"221","author":"T G\u00fcng\u00f6r","year":"2021","unstructured":"G\u00fcng\u00f6r, T. et al. New nimesulide derivatives with amide\/sulfonamide moieties: Selective COX-2 inhibition and antitumor effects. Eur. J. Med. Chem. 221, 113566. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113566 (2021).","journal-title":"Eur. J. Med. Chem."},{"key":"50210_CR32","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/BF03226418","volume":"30","author":"\u015eG K\u00fc\u00e7\u00fckg\u00fczel","year":"2005","unstructured":"K\u00fc\u00e7\u00fckg\u00fczel, \u015e. G., K\u00fc\u00e7\u00fckg\u00fczel, I., Oral, B., Sezen, S. & Rollas, S. Detection of nimesulide metabolites in rat plasma and hepatic subcellular fractions by HPLC-UV\/DAD and LC-MS\/MS studies. Eur. J. Drug Metab. Pharmacokinet. 30, 127\u2013134. https:\/\/doi.org\/10.1007\/BF03226418 (2005).","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"50210_CR33","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1007\/s00204-021-03000-8","volume":"95","author":"F Bessone","year":"2021","unstructured":"Bessone, F. et al. Serious liver injury induced by nimesulide: An international collaborative study. Arch. Toxicol. 95, 1475\u20131487. https:\/\/doi.org\/10.1007\/s00204-021-03000-8 (2021).","journal-title":"Arch. Toxicol."},{"key":"50210_CR34","doi-asserted-by":"publisher","first-page":"633","DOI":"10.2165\/00002018-200225090-00003","volume":"25","author":"UA Boelsterli","year":"2002","unstructured":"Boelsterli, U. A. Mechanisms of NSAID-induced hepatotoxicity: Focus on nimesulide. Drug Saf. 25, 633\u2013648. https:\/\/doi.org\/10.2165\/00002018-200225090-00003 (2002).","journal-title":"Drug Saf."},{"key":"50210_CR35","first-page":"1410","volume":"7","author":"SH Bae","year":"2001","unstructured":"Bae, S. H. et al. Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398. Clin. Cancer Res. 7, 1410\u20131418 (2001).","journal-title":"Cancer Res."},{"key":"50210_CR36","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1007\/bf03401977","volume":"7","author":"K Meyer-Siegler","year":"2001","unstructured":"Meyer-Siegler, K. COX-2 specific inhibitor, NS-398, increases macrophage migration inhibitory factor expression and induces neuroendocrine differentiation in C4-2b prostate cancer cells. Mol. Med. 7, 850\u2013860. https:\/\/doi.org\/10.1007\/bf03401977 (2001).","journal-title":"Mol. Med."},{"key":"50210_CR37","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1080\/10428190400015691","volume":"46","author":"M Zhang","year":"2005","unstructured":"Zhang, M. et al. Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via a Bcl-2-independent pathway. Leuk. Lymphoma. 46, 425\u2013433. https:\/\/doi.org\/10.1080\/10428190400015691 (2005).","journal-title":"Leuk. Lymphoma"},{"key":"50210_CR38","first-page":"5767","volume":"60","author":"RF Souza","year":"2000","unstructured":"Souza, R. F., Shewmake, K., Beer, D. G., Cryer, B. & Spechler, S. J. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Cancer Res. 60, 5767\u20135772 (2000).","journal-title":"Cancer Res."},{"key":"50210_CR39","doi-asserted-by":"publisher","first-page":"108850","DOI":"10.1016\/j.bioorg.2025.108850","volume":"164","author":"K Birg\u00fcl","year":"2025","unstructured":"Birg\u00fcl, K. et al. Investigation of novel nimesulide derivatives against breast cancer. Bioorg. Chem. 164, 108850. https:\/\/doi.org\/10.1016\/j.bioorg.2025.108850 (2025).","journal-title":"Bioorg. Chem."},{"key":"50210_CR40","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1007\/s11030-021-10221-7","volume":"26","author":"S Albayati","year":"2022","unstructured":"Albayati, S., Uba, A. I. & Yelek\u00e7i, K. Potential inhibitors of methionine aminopeptidase type II identified via structure-based pharmacophore modeling. Mol. Divers. 26, 1005\u20131016. https:\/\/doi.org\/10.1007\/s11030-021-10221-7 (2022).","journal-title":"Mol. Divers."},{"key":"50210_CR41","doi-asserted-by":"publisher","first-page":"4505","DOI":"10.1038\/s41388-025-03594-8","volume":"44","author":"L Wu","year":"2025","unstructured":"Wu, L. et al. METAP2 inhibits K48-linked ubiquitination of YTHDF2 to promote ovarian cancer progression. Oncogene 44, 4505\u20134519. https:\/\/doi.org\/10.1038\/s41388-025-03594-8 (2025).","journal-title":"Oncogene"},{"key":"50210_CR42","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1007\/s13346-022-01187-6","volume":"13","author":"R Esa","year":"2023","unstructured":"Esa, R. et al. Newly synthesized methionine aminopeptidase 2 inhibitor hinders tumor growth. Drug Deliv Transl Res. 13, 1170\u20131182. https:\/\/doi.org\/10.1007\/s13346-022-01187-6 (2023).","journal-title":"Drug Deliv Transl Res."},{"key":"50210_CR43","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.tips.2021.07.004","volume":"42","author":"A Goya Grocin","year":"2021","unstructured":"Goya Grocin, A., Kallemeijn, W. W. & Tate, E. W. Targeting methionine aminopeptidase 2 in cancer, obesity and autoimmunity. Trends Pharmacol. Sci. 42, 870\u2013882. https:\/\/doi.org\/10.1016\/j.tips.2021.07.004 (2021).","journal-title":"Trends Pharmacol. Sci."},{"key":"50210_CR44","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1158\/1535-7163.MCT-23-0574","volume":"23","author":"P Cornelius","year":"2024","unstructured":"Cornelius, P. et al. Pharmacological characterization of SDX-7320\/evexomostat: a novel methionine aminopeptidase type 2 inhibitor with anti-tumor and anti-metastatic activity. Mol. Cancer Ther. 23, 595\u2013605. https:\/\/doi.org\/10.1158\/1535-7163.MCT-23-0574 (2024).","journal-title":"Mol. Cancer Ther."},{"key":"50210_CR45","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1158\/2767-9764.CRC-23-0048","volume":"3","author":"MA Carducci","year":"2023","unstructured":"Carducci, M. A. et al. A first-in-human, dose-escalation study of the methionine aminopeptidase 2 inhibitor M8891 in patients with advanced solid tumors. Cancer Res. Commun. 3, 1638\u20131647. https:\/\/doi.org\/10.1158\/2767-9764.CRC-23-0048 (2023).","journal-title":"Cancer Res. Commun."},{"key":"50210_CR46","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1158\/0008-5472.CAN-20-2969","volume":"81","author":"J Xie","year":"2021","unstructured":"Xie, J. et al. In vivo imaging of methionine aminopeptidase II for prostate cancer risk stratification. Cancer Res. 81, 2510\u20132521. https:\/\/doi.org\/10.1158\/0008-5472.CAN-20-2969 (2021).","journal-title":"Cancer Res."},{"key":"50210_CR47","first-page":"1989","volume":"5","author":"P Bhargava","year":"1999","unstructured":"Bhargava, P. et al. A phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancer. Clin. Cancer Res. 5, 1989\u20131995 (1999).","journal-title":"Clin. Cancer Res."},{"key":"50210_CR48","doi-asserted-by":"publisher","first-page":"108850","DOI":"10.1016\/j.bioorg.2025.108850","volume":"164","author":"K Birg\u00fcl","year":"2025","unstructured":"Birg\u00fcl, K. et al. Investigation of novel nimesulide derivatives against breast cancer. Bioorg. Chem. 164, 108850. https:\/\/doi.org\/10.1016\/j.bioorg.2025.108850 (2025).","journal-title":"Bioorg. Chem."},{"key":"50210_CR49","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jsps.2022.03.004","volume":"30","author":"LA Jaragh-Alhadad","year":"2022","unstructured":"Jaragh-Alhadad, L. A. & Ali, M. S. Methoxybenzamide derivative of nimesulide from anti-fever to anti-cancer: Chemical characterization and cytotoxicity. Saudi Pharm. J. 30, 485\u2013493. https:\/\/doi.org\/10.1016\/j.jsps.2022.03.004 (2022).","journal-title":"Saudi Pharm. J."},{"key":"50210_CR50","doi-asserted-by":"publisher","unstructured":"Jaragh-Alhadad, L. A. & Ali, M. S. Nimesulide derivatives reduced cell proliferation against breast and ovarian cancer: Synthesis, characterization, biological assessment and crystal structure. Kuwait J. Sci. 49. https:\/\/doi.org\/10.48129\/kjs.16735 (2022).","DOI":"10.48129\/kjs.16735"},{"key":"50210_CR51","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2165\/00003495-199300461-00005","volume":"46","author":"R Maffei Facino","year":"1993","unstructured":"Maffei Facino, R., Carini, M. & Aldini, G. Antioxidant activity of nimesulide and its main metabolites. Drugs 46, 15\u201321. https:\/\/doi.org\/10.2165\/00003495-199300461-00005 (1993).","journal-title":"Drugs"},{"key":"50210_CR52","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1185\/030079907X223486","volume":"23","author":"W Kullich","year":"2007","unstructured":"Kullich, W., Fagerer, N. & Schwann, H. Effect of the NSAID nimesulide on the radical scavenger glutathione S-transferase in patients with osteoarthritis of the knee. Curr. Med. Res. Opin. 23, 1981\u20131986. https:\/\/doi.org\/10.1185\/030079907X223486 (2007).","journal-title":"Curr. Med. Res. Opin."},{"key":"50210_CR53","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.2174\/1871520619666190227174137","volume":"19","author":"B B\u00fclb\u00fcl","year":"2019","unstructured":"B\u00fclb\u00fcl, B. & K\u00fc\u00e7\u00fckg\u00fczel, \u0130. Microsomal prostaglandin E2 synthase-1 as a new macromolecular drug target in the prevention of inflammation and cancer. Anticancer Agents Med. Chem. 19, 1205\u20131222. https:\/\/doi.org\/10.2174\/1871520619666190227174137 (2019).","journal-title":"Anticancer Agents Med. Chem."},{"key":"50210_CR54","doi-asserted-by":"publisher","first-page":"136813","DOI":"10.1016\/j.molstruc.2023.136813","volume":"1295","author":"Y Biliz","year":"2024","unstructured":"Biliz, Y. et al. Synthesis of new pyrazolidines by [3\u2009+\u20092] cycloaddition: Anticancer, antioxidant activities and molecular docking studies. J. Mol. Struct. 1295, 136813. https:\/\/doi.org\/10.1016\/j.molstruc.2023.136813 (2024).","journal-title":"J. Mol. Struct."},{"key":"50210_CR55","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/jccs.201800126","volume":"66","author":"B Hasdemir","year":"2019","unstructured":"Hasdemir, B., Ya\u015fa, H. & Akkam\u0131\u015f, Y. Synthesis and antioxidant activities of novel N-aryl (and N-alkyl) \u03b3- and \u03b4-imino esters and ketimines. J. Chin. Chem. Soc. 66, 197\u2013204. https:\/\/doi.org\/10.1002\/jccs.201800126 (2019).","journal-title":"J. Chin. Chem. Soc."},{"key":"50210_CR56","doi-asserted-by":"publisher","first-page":"20073","DOI":"10.1021\/acsomega.3c02361","volume":"8","author":"Y Biliz","year":"2023","unstructured":"Biliz, Y. et al. Novel N-acyl hydrazone compounds as promising anticancer agents: Synthesis and molecular docking studies. ACS Omega. 8, 20073\u201320084. https:\/\/doi.org\/10.1021\/acsomega.3c02361 (2023).","journal-title":"ACS Omega"},{"key":"50210_CR57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1515\/tjb-2017-0355","volume":"44","author":"O Cevik","year":"2019","unstructured":"Cevik, O., Turut, F. A., Acidereli, H. & Yildirim, S. Cyclosporine-A induces apoptosis in human prostate cancer cells PC3 and DU145 via downregulation of COX-2 and upregulation of TGF\u03b2. Turk. J. Biochem. 44, 47\u201354. https:\/\/doi.org\/10.1515\/tjb-2017-0355 (2019).","journal-title":"Turk. J. Biochem."},{"key":"50210_CR58","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.55730\/1300-0527.3411","volume":"46","author":"GM Demirbolat","year":"2022","unstructured":"Demirbolat, G. M., Erdo\u011fan, \u00d6., Co\u015fkun, G. P. & \u00c7evik, \u00d6. PEG4000 modified liposomes enhance the solubility of quercetin and improve liposome functionality: In vitro characterization and cellular efficacy. Turk. J. Chem. 46, 1011\u20131023. https:\/\/doi.org\/10.55730\/1300-0527.3411 (2022).","journal-title":"Turk. J. Chem."},{"key":"50210_CR59","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s11030-022-10591-6","volume":"28","author":"D Uslu","year":"2024","unstructured":"Uslu, D., Abas, B. I., Demirbolat, G. M. & Cevik, O. Effect of platelet exosomes loaded with doxorubicin as a targeted therapy on triple-negative breast cancer cells. Mol. Divers. 28, 449\u2013460. https:\/\/doi.org\/10.1007\/s11030-022-10591-6 (2024).","journal-title":"Mol. Divers."},{"key":"50210_CR60","doi-asserted-by":"publisher","first-page":"e70079","DOI":"10.1002\/jbt.70079","volume":"38","author":"F Tok","year":"2024","unstructured":"Tok, F. et al. Synthesis, biological evaluation and in silico studies of novel urea\/thiourea derivatives of lenalidomide. J. Biochem. Mol. Toxicol. 38, e70079. https:\/\/doi.org\/10.1002\/jbt.70079 (2024).","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"50210_CR61","doi-asserted-by":"publisher","first-page":"e22542","DOI":"10.1002\/jbt.22542","volume":"34","author":"O Cevik","year":"2020","unstructured":"Cevik, O. et al. Cabazitaxel exhibits more favorable molecular changes compared to other taxanes in androgen-independent prostate cancer cells. J. Biochem. Mol. Toxicol. 34, e22542. https:\/\/doi.org\/10.1002\/jbt.22542 (2020).","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"50210_CR62","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/S0006-291X(03)01144-6","volume":"307","author":"JY Li","year":"2003","unstructured":"Li, J. Y. et al. Specificity for inhibitors of metal-substituted methionine aminopeptidase. Biochem. Biophys. Res. Commun. 307, 172\u2013179. https:\/\/doi.org\/10.1016\/S0006-291X(03)01144-6 (2003).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"50210_CR63","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10456-004-6089-7","volume":"7","author":"T Garrabrant","year":"2004","unstructured":"Garrabrant, T. et al. Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP2). Angiogenesis 7, 91\u201396. https:\/\/doi.org\/10.1007\/s10456-004-6089-7 (2004).","journal-title":"Angiogenesis"},{"key":"50210_CR64","unstructured":"Dassault Syst\u00e8mes. BIOVIA Discovery Studio 2017 R2: A comprehensive predictive science application for the life sciences (Dassault Syst\u00e8mes, 2017)."},{"key":"50210_CR65","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O., Olson, A. J., AutoDock & Vina Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem. 31, 455\u2013461. https:\/\/doi.org\/10.1002\/jcc.21334 (2010).","journal-title":"J. Comput. Chem."},{"key":"50210_CR66","doi-asserted-by":"publisher","first-page":"4100","DOI":"10.1080\/07391102.2020.1774417","volume":"39","author":"A Al-Obaidi","year":"2021","unstructured":"Al-Obaidi, A., Elmezayen, A. D. & Yelek\u00e7i, K. Homology modeling of human GABA-AT and design of novel potent inhibitors via computer-aided drug design. J. Biomol. Struct. Dyn. 39, 4100\u20134110. https:\/\/doi.org\/10.1080\/07391102.2020.1774417 (2021).","journal-title":"J. Biomol. Struct. Dyn."},{"key":"50210_CR67","doi-asserted-by":"publisher","first-page":"e35020","DOI":"10.1016\/j.heliyon.2024.e35020","volume":"10","author":"NM Mert","year":"2024","unstructured":"Mert, N. M., Erdogan, B. & Yelek\u00e7i, K. Repurposing of known drugs to identify selective HDAC6 inhibitors via in silico and molecular modeling approaches. Heliyon 10, e35020. https:\/\/doi.org\/10.1016\/j.heliyon.2024.e35020 (2024).","journal-title":"Heliyon"},{"key":"50210_CR68","doi-asserted-by":"publisher","unstructured":"Bowers, K. J. et al. Scalable algorithms for molecular dynamics simulations on commodity clusters. In Proc. ACM\/IEEE Conf. Supercomputing (SC\u201906) 84 (2006). https:\/\/doi.org\/10.1145\/1188455.1188544.","DOI":"10.1145\/1188455.1188544"},{"key":"50210_CR69","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","volume":"10","author":"S Genheden","year":"2015","unstructured":"Genheden, S. & Ryde, U. The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities. Expert Opin. Drug Discov. 10, 449\u2013461. https:\/\/doi.org\/10.1517\/17460441.2015.1032936 (2015).","journal-title":"Expert Opin. Drug Discov"},{"key":"50210_CR70","doi-asserted-by":"publisher","first-page":"431","DOI":"10.2165\/00003495-199448030-00008","volume":"48","author":"R Davis","year":"1994","unstructured":"Davis, R., Brogden, R. N. & Nimesulide An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs 48, 431\u2013454. https:\/\/doi.org\/10.2165\/00003495-199448030-00008 (1994).","journal-title":"Drugs"},{"key":"50210_CR71","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0167-4838(99)00271-X","volume":"1477","author":"WT Lowther","year":"2000","unstructured":"Lowther, W. T. & Matthews, B. W. Structure and function of the methionine aminopeptidases. Biochim. Biophys. Acta. 1477, 157\u2013167 (2000).","journal-title":"Biochim. Biophys. Acta"},{"key":"50210_CR72","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1073\/pnas.0708766105","volume":"105","author":"J Wang","year":"2008","unstructured":"Wang, J. et al. Correlation of tumor growth suppression and methionine aminopeptidase-2 activity blockade using an orally active inhibitor. Proc. Natl. Acad. Sci. USA. 105, 1838\u20131843. https:\/\/doi.org\/10.1073\/pnas.0708766105 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"50210_CR73","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1158\/1535-7163.MCT-23-0574","volume":"23","author":"P Cornelius","year":"2024","unstructured":"Cornelius, P. et al. Pharmacological characterization of SDX-7320\/evexomostat, a methionine aminopeptidase type 2 inhibitor with anti-tumor and anti-metastatic activity. Mol. Cancer Ther. 23, 595\u2013605. https:\/\/doi.org\/10.1158\/1535-7163.MCT-23-0574 (2024).","journal-title":"Mol. Cancer Ther."},{"key":"50210_CR74","first-page":"7861","volume":"63","author":"J Wang","year":"2003","unstructured":"Wang, J. et al. Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2. Cancer Res. 63, 7861\u20137869 (2003).","journal-title":"Cancer Res."},{"key":"50210_CR75","doi-asserted-by":"publisher","first-page":"6427","DOI":"10.1073\/pnas.97.12.6427","volume":"97","author":"Y Zhang","year":"2000","unstructured":"Zhang, Y. et al. Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1\/CIP1. Proc. Natl. Acad. Sci. USA. 97, 6427\u20136432. https:\/\/doi.org\/10.1073\/pnas.97.12.6427 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"50210_CR76","doi-asserted-by":"publisher","first-page":"12782","DOI":"10.1073\/pnas.97.23.12782","volume":"97","author":"JR Yeh","year":"2000","unstructured":"Yeh, J. R., Mohan, R. & Crews, C. M. The antiangiogenic agent TNP-470 requires p53 and p21CIP\/WAF for endothelial cell growth arrest. Proc. Natl. Acad. Sci. USA. 97, 12782\u201312787. https:\/\/doi.org\/10.1073\/pnas.97.23.12782 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50210-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50210-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50210-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:10:31Z","timestamp":1781824231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50210-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":76,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["50210"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-50210-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"18 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19076"}}